Stereochemistry: Chirality, R/S and Z/E

What is stereochemistry?

Two molecules can have the same atoms joined in the same order and still be different, because the atoms are arranged differently in space. Studying this is stereochemistry. Molecules that differ only in 3D arrangement are called stereoisomers.

Chirality

An object is chiral if it cannot be placed on top of its mirror image. Your hand is the classic case. In molecules, the usual cause is a carbon joined to four different groups (a chiral centre, often marked with a star). The two mirror forms are called enantiomers.

Test: draw the mirror image and try to overlap it by turning. If you cannot, the molecule is chiral. If two of the four groups are the same, the carbon is not chiral.

CIP priority rules

To give a clear name to each 3D shape, chemists use the Cahn–Ingold–Prelog (CIP) rules. They put the four groups in an order from 1 (highest) to 4 (lowest).

1. Look at the atom directly joined to the chiral carbon. Higher atomic number gets higher priority. So I > Br > Cl > S > F > O > N > C > H.
2. If two atoms tie, move one step outward and compare the atoms they carry, set by set, until a difference appears.
3. A double bond counts as two single bonds to the same atom (it is copied once). For example, C=O counts as C joined to O and a duplicate O.

Example: in CHBrClF the order is Br (35) > Cl (17) > F (9) > H (1).

R and S configuration

Once the groups are ranked, follow three steps.

1. Turn the molecule so the lowest priority (4) points away from you.
2. Look at the other three. Go from 1 to 2 to 3.
3. Clockwise = R (rectus, right). Anticlockwise = S (sinister, left).

Swapping any two groups changes R to S. If the lowest group points towards you instead, read the direction and then reverse the answer.

Enantiomers have opposite labels (one R, one S). They have the same melting point and boiling point, but they turn plane-polarised light in opposite directions. The R/S letter does not tell you which way the light turns; that must be measured.

Z/E isomerism

A C=C double bond is stiff, so groups on each carbon cannot swap sides. This gives geometric isomers. The simple names cis and trans work when each carbon has one identical group. For harder cases we use Z and E.

1. On each carbon of the double bond, rank the two groups with the CIP rules.
2. If the two high-priority groups are on the same side: Z (German zusammen, together).
3. If they are on opposite sides: E (entgegen, opposite).

Z and E isomers are different compounds, with different boiling points and often different smells and uses.

Try it: make your own chiral model

Take a ball of clay and four toothpicks. Colour the toothpick tips with four different colours (stick on coloured paper). Push them into the ball in a pyramid shape. Now build the mirror twin and try to line the colours up by turning. You cannot. Next, use two tips of the same colour: now the twin fits. In the 3D, use the buttons in the last step to swap groups and watch R and S change.

Key formulas and definitions

• Chiral carbon: 4 different groups on one sp3 carbon
• CIP priority: higher atomic number = higher priority (I > Br > Cl > S > F > O > N > C > H)
• R: lowest priority away, 1 → 2 → 3 clockwise; S: anticlockwise
• Swap any two groups: R ↔ S
• Z: higher-priority groups on the same side; E: on opposite sides
• Number of stereoisomers with n chiral centres ≤ 2ⁿ

Worked examples

Common mistakes

• Reading R or S while the lowest priority group is pointing towards you. Turn it away first, or reverse the answer.
• Ranking by size or mass of the whole group instead of the atomic number of the first atom joined to carbon.
• Calling a carbon chiral when two of its groups are the same.
• Thinking R means "turns light right". R/S is a naming rule; the light direction is measured separately.